title: Innate immunity in an in vitro murine blastocyst model using embryonic and trophoblast stem cells.
abstract: The immune system has two broad components-innate and adaptive immunity. Adaptive immunity becomes established only after the onset of hematopoiesis, whereas the innate immune system may be actively protecting organisms from microbial invasion much earlier in development. Here, we address the question of whether the innate immune system functions in the early-stage embryo, i.e., the blastocyst. The innate immune system was studied by using in vitro blastocyst models, e.g., embryonic stem (ES) and trophoblast stem (TS) cell cultures. The expression of Toll-like receptors (TLR)-2, -3, and -5 could be detected in both ES and TS cells. The expression of interferon (IFN)-β was induced by the addition of polyinosinic:polycytidylic acid [poly(I:C)] in TS cells, but not ES cells, although TLR-3 was expressed at the same level in both cell types. In turn, ES cells responded to IFN-β exposure by expressing IFN-induced anti-viral genes, e.g., RNA-dependent protein kinase and 2', 5'-oligoadenylate synthetase (OAS). Neither a reduction in ES cell proliferation nor cell death in these cultures was observed after IFN-β stimulation. Furthermore, OAS1a expression was induced in ES/TS co-cultures after poly(I:C) stimulation, but was not induced when either cell type was cultured alone. In conclusion, TS cells react to poly(I:C) stimulation by producing IFN-β, which induces IFN-inducible genes in ES cells. This observation suggests that the trophectoderm, the outer layer of the blastocyst, may respond to viral infection, and then induce anti-viral gene expression via IFN-β signaling to the blastocyst inner cell mass.
authors.affiliation: Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 B51, Nagatsuta-cho, Midori-ku, Yokohama-shi, Kanagawa 226-8501, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Aikawa
authors.affiliation: Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 B51, Nagatsuta-cho, Midori-ku, Yokohama-shi, Kanagawa 226-8501, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Tamai
authors.affiliation: Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 B51, Nagatsuta-cho, Midori-ku, Yokohama-shi, Kanagawa 226-8501, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Mitamura
authors.affiliation: Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 B51, Nagatsuta-cho, Midori-ku, Yokohama-shi, Kanagawa 226-8501, Japan.
authors.forename: Fakhria
authors.initials: F
authors.lastname: Itmainati
authors.affiliation: Department of Medicine and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Rm 511 Papanicolaou Building, 1550 NW 10th Ave, Miami, FL 33136, USA.
authors.forename: Glen N
authors.initials: GN
authors.lastname: Barber
authors.affiliation: Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 B51, Nagatsuta-cho, Midori-ku, Yokohama-shi, Kanagawa 226-8501, Japan. Electronic address: ytagawa@bio.titech.ac.jp.
authors.forename: Yoh-ichi
authors.initials: Y
authors.lastname: Tagawa
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001755:Blastocyst / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D007113:Immunity, Innate; D007369:Interferon Inducers / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013234:Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D007369:Interferon Inducers; D012333:RNA, Messenger; D051196:Toll-Like Receptor 3; D016899:Interferon-beta
keywords: Blastocyst; Embryonic stem cell; Innate immunity; Toll-like receptors; Trophoblast stem cell; Type-I interferon